In this depiction of in silico retrograde staining, a digital reconstruction of neocortical microcircuitry, the presynaptic neurons of a layer 2/3 nest basket cell (red) are stained in blue. Only immediate neighboring presynaptic neurons are shown. [© BBP/EPFL 2015]
In this depiction of in silico retrograde staining, a digital reconstruction of neocortical microcircuitry, the presynaptic neurons of a layer 2/3 nest basket cell (red) are stained in blue. Only immediate neighboring presynaptic neurons are shown. [© BBP/EPFL 2015]

It’s a piece of rat brain containing about 30,000 neurons and 40 million synaptic connections, and there’s nothing remarkable about it, except that it isn’t real. It’s a digital reconstruction—a representation of a one-third cubic millimeter of rat neocortex—and it seems to work like the real thing.

Needless to say, its many creators are proud. They include 82 scientists and engineers from around the world, collaborators who are aware that their reconstruction represents the culmination of 20 years of biological experimentation and 10 years of computational science work. They are also aware that their work is controversial. It was criticized last year in an open letter. Signed by hundreds of neuroscientists, the letter argued that attempts to digitally reconstruct brain tissue were premature and represented an “overly narrow” approach that risked a misallocation of resources.

Undaunted, the investigators, led by scientists of the École Polytechnique Fédérale de Lausanne (EPFL), ran simulations on supercomputers to show that the electrical behavior of the virtual brain tissue matched the behavior of real rat neocortical tissue. Even though the digital reconstruction was not designed to reproduce any specific circuit phenomenon, a variety of experimental findings emerged. One such simulation examined how different types of neuron would respond if fibers coming into the neocortex were to convey signals encoding touch sensations. The researchers found that the responses of the different types of neurons in the digital reconstruction were very similar to those that had been previously observed in the laboratory.

These findings appeared October 8 in the journal Cell, in an article entitled, “Reconstruction and Simulation of Neocortical Microcircuitry.” This article also described how additional simulations revealed novel insights into the functioning of the neocortex.

“[We] find a spectrum of network states with a sharp transition from synchronous to asynchronous activity, modulated by physiological mechanisms,” wrote the authors. “The spectrum of network states, dynamically reconfigured around this transition, supports diverse information processing strategies.”

The authors even suggested that their work represents the first step toward the digital reconstruction and simulation of a whole brain. “They delivered what they promised,” said Patrick Aebischer, president of EPFL. This statement appeared in an EPFL press release that also indicated that the EPFL, together with the Swiss government, took the “bold step of funding the ambitious and controversial Blue Brain Project.”

The Blue Brain project is the simulation core of the Human Brain Project, a decade-long effort that is being allocated more than $1 billion.

“While a long way from the whole brain, the study demonstrates that it is feasible to digitally reconstruct and simulate brain tissue,” the release continued. “It is a first step and a significant contribution to Europe’s Human Brain Project, which Henry Markram founded, and where EPFL is the coordinating partner.”

Idan Segev, a senior author, sees the paper as building on the pioneering work of the Spanish anatomist, Ramon y Cajal from more than 100 years ago. “Ramon y Cajal began drawing every type of neuron in the brain by hand. He even drew in arrows to describe how he thought the information was flowing from one neuron to the next. Today, we are doing what Cajal would be doing with the tools of the day—building a digital representation of the neurons and synapses and simulating the flow of information between neurons on supercomputers. Furthermore, the digitization of the tissue allows the data to be preserved and reused for future generations.”

Now that the Blue Brain team has published the experimental results and the digital reconstruction, other scientists will be able to use the data and reconstruction to test other theories of brain function.

“The reconstruction is a first draft, it is not complete and it is not yet a perfect digital replica of the biological tissue,” explained Henry Markram. In fact, the current version explicitly leaves out many important aspects of the brain, such as glia, blood vessels, gap-junctions, plasticity, and neuromodulation. According to Sean Hill, a senior author: “The job of reconstructing and simulating the brain is a large-scale collaborative one, and the work has only just begun. The Human Brain Project represents the kind of collaboration that is required.”








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